Applied Biochemistry and Biotechnology

, Volume 186, Issue 1, pp 1–11 | Cite as

Hypericum japonicum: a Double-Headed Sword to Combat Vector Control and Cancer

  • Sreedev Puthur
  • A. N Anoopkumar
  • Sharrel Rebello
  • Embalil Mathachan AneeshEmail author


Mosquito control with naturally derived herbal insecticides has gained much momentum, with the increased insecticide resistance of vectors and the multiple infectious diseases spread by them. Yet, recent studies also suggest that mosquitoes could probably transmit some cancerous cells or cancer-causing viruses from one individual to another between their blood meals. The current research thus focused on the screening and characterization of novel plants with both mosquitocidal and anticancerous properties. Accordingly, different solvent extracts of Hypericum japonicum, a key plant in Chinese medicine, were screened for its larvicidal efficacy using the fourth instar larvae of Aedes aegypti (major vector of Dengue and chikungunya). Methanolic extracts of the plant showed effective larvicidal property with LC50 7.37 ppm and LC9011.59 ppm values. The anticancerous property of the plant extract was also evaluated by in vitro cytotoxicity assay against Daltons Lymphoma Ascites (DLA) cells. The results indicated that H. japonicum plant extracts at very low concentrations of LC500.95 ppm and LC901.85 ppm were potent cytotoxic agents. To the best of our knowledge, this is the first and the foremost report of Hypericum japonicum as a potent mosquitocidal and anticancerous agent. Identification and characterization of such plant-derived bioactive plants thus could serve as a double-headed sword against the spread of infectious diseases and cancer.


Aedes aegypti Hypericum japonicum Larval bioassay Cytotoxicity DLA cells 


A. aegypti

Aedes aegypti


Lower confidence limit


Upper confidence limit


Lethal Dose


Daltons Lymphoma Ascites cells



The authors are thankful to the Principal of St. Joseph’s College for the laboratory facilities provided. We acknowledge UGC, Govt. of India, and Kerala State Council for Science Technology and Environment (KSCSTE) for funds under Major Research Project (No. 27/SRSLS/2013/CSTE).

Compliance with Ethical Standards

Conflict of Interests

The authors declare that they have no conflict of interests.


  1. 1.
    Abbott, W. S. (1925). A method of computing the effectiveness of an insecticide. Journal of Economic Entomology, 18(2), 265–267.CrossRefGoogle Scholar
  2. 2.
    Aneesh, E.M., & Vijayan, V. (2010). Laboratory selection of carbofuran tolerant line of Culex quinquefasciatus Say, the filarial vector at Mysore. Journal of communicable Diseases, 42, 201–207.Google Scholar
  3. 3.
    Anoopkumar, A., Puthur, S., Varghese, P., Rebello, S., & Aneesh, E. M. (2017). Life cycle, bio-ecology and DNA barcoding of mosquitoes Aedes aegypti (Linnaeus) and Aedes albopictus (Skuse). The Journal of Communicable Diseases, 49.Google Scholar
  4. 4.
    Aparna Ravi, M. G., Mudiganti Ram Krishna Rao, Kalaivani, V. S. Kalaiselvi, K. Prabhu, Shruthi Dinakar, G. V. Rao. (2015) GC MS analysis of an Ayurvedic medicine “Ashokarishtam” Der Pharmacia Lettre, 7, 45–52.Google Scholar
  5. 5.
    Arufe, M. I., Arellano, J. M., García, L., Albendín, G., & Sarasquete, C. (2007). Cholinesterase activity in gilthead seabream (Sparus aurata) larvae: characterization and sensitivity to the organophosphate azinphosmethyl. Aquatic Toxicology, 84(3), 328–336.CrossRefPubMedGoogle Scholar
  6. 6.
    Banfield, W. G., Woke, P. A., & Mackay, C. M. (1966). Mosquito transmission of lymphomas. Cancer, 19(10), 1333–1336.CrossRefPubMedGoogle Scholar
  7. 7.
    Banfield, W. G., Woke, P. A., MacKay, C. M., & Cooper, H. L. (1965). Mosquito transmission of a reticulum cell sarcoma of hamsters. Science, 148(3674), 1239–1240.CrossRefPubMedGoogle Scholar
  8. 8.
    Benelli, G., Iacono, A. L., Canale, A., & Mehlhorn, H. (2016). Mosquito vectors and the spread of cancer: an overlooked connection? Parasitology Research, 115(6), 2131–2137.CrossRefPubMedGoogle Scholar
  9. 9.
    Bessette, S. (2007) Pesticidal compositions containing isopropyl-containing compounds as pesticidally active ingredients. Google Patents.Google Scholar
  10. 10.
    Choochote, W., Chaithong, U., Kamsuk, K., Rattanachanpichai, E., Jitpakdi, A., Tippawangkosol, P., Chaiyasit, D., Champakaew, D., Tuetun, B., & Pitasawat, B. (2006). Adulticidal activity against Stegomyia aegypti (Diptera: Culicidae) of three Piper spp. Revista do Instituto de Medicina Tropical de São Paulo, 48(1), 33–37.CrossRefPubMedGoogle Scholar
  11. 11.
    Fradin, M. S., & Day, J. F. (2002). Comparative efficacy of insect repellents against mosquito bites. New England Journal of Medicine, 347(1), 13–18.CrossRefPubMedGoogle Scholar
  12. 12.
    Group, W. S. (2006). Malaria vector control and personal protection. World Health Organization Technical Report Series, 936, 1.Google Scholar
  13. 13.
    Gubler, D. J. (1998). Resurgent vector-borne diseases as a global health problem. Emerging Infectious Diseases, 4(3), 442–450.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Hales, S., De Wet, N., Maindonald, J., & Woodward, A. (2002). Potential effect of population and climate changes on global distribution of dengue fever: an empirical model. The Lancet, 360(9336), 830–834.CrossRefGoogle Scholar
  15. 15.
    Hu, L., Xue, Y., Zhang, J., Zhu, H., Chen, C., Li, X.-N., Liu, J., Wang, Z., Zhang, Y., & Zhang, Y. (2016). (±)-Japonicols A-D, acylphloroglucinol-based meroterpenoid enantiomers with anti-KSHV activities from Hypericum japonicum. Journal of Natural Products, 79(5), 1322–1328.CrossRefPubMedGoogle Scholar
  16. 16.
    Ishiguro, K., Yamaki, M., Kashihara, M., & Takagi, S. (1986). Sarothralen A and B, new antibiotic compounds from Hypericum japonicum. Planta Medica, 52(04), 288–290.CrossRefGoogle Scholar
  17. 17.
    Jeanne, R. L. and Henderson, G. (1992) Non-insecticidal insect repellent. Google Patents.Google Scholar
  18. 18.
    Katoch, R., Sethi, A., Thakur, N., & Murdock, L. L. (2013). RNAi for insect control: current perspective and future challenges. Applied Biochemistry and Biotechnology, 171(4), 847–873.CrossRefPubMedGoogle Scholar
  19. 19.
    Killeen, G. F., Fillinger, U., & Knols, B. G. (2002). Advantages of larval control for African malaria vectors: low mobility and behavioural responsiveness of immature mosquito stages allow high effective coverage. Malaria Journal, 1(1), 8.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ko, W., Kang, T., Kim, N., Lee, S., Kim, Y., Ko, G., Ryu, S., & Lee, B. (2000). Lavandulylflavonoids: a new class of in vitro apoptogenic agents from Sophora flavescens. Toxicology In Vitro, 14(5), 429–433.CrossRefPubMedGoogle Scholar
  21. 21.
    Komalamisra, N., Trongtokit, Y., Rongsriyam, Y., & Apiwathnasorn, C. (2005). Screening for larvicidal activity in some Thai plants against four mosquito vector species. The Southeast Asian Journal of Tropical Medicine and Public Health, 36(6), 1412–1422.PubMedGoogle Scholar
  22. 22.
    Lee, S. E. (2000) Mosquito larvicidal activity of pipernonaline, a piperidine alkaloid derived from long pepper, Piper longum. Journal of the American Mosquito Control Association- Mosquito News, 16, 245–247, 3.Google Scholar
  23. 23.
    Lehrer, S. (2010). Anopheles mosquito transmission of brain tumor. Medical Hypotheses, 74(1), 167–168.CrossRefPubMedGoogle Scholar
  24. 24.
    Lehrer, S. (2010). Association between malaria incidence and all cancer mortality in fifty US States and the District of Columbia. Anticancer Research, 30(4), 1371–1373.PubMedGoogle Scholar
  25. 25.
    Liu, L.-S., Liu, M.-H., & He, J.-Y. (2014). Hypericum japonicum Thunb. ex Murray: phytochemistry, pharmacology, quality control and pharmacokinetics of an important herbal medicine. Molecules, 19(12), 10733–10754.CrossRefPubMedGoogle Scholar
  26. 26.
    Madhu, S., & Vijayan, V. (2010). Evaluation of the larvicidal efficacy of extracts from three plants and their synergistic action with propoxur against larvae of the filarial vector Culex quinquefasciatus (Say). Toxicological & Environmental Chemistry, 92(1), 115–126.CrossRefGoogle Scholar
  27. 27.
    Madhu, S., Vijayan, V., & Shaukath, A. (2011). Bioactivity guided isolation of mosquito larvicide from Piper longum. Asian Pacific Journal of Tropical Medicine, 4(2), 112–116.CrossRefPubMedGoogle Scholar
  28. 28.
    Madhumathy, A., Aivazi, A.-A., & Vijayan, V. (2007). Larvicidal efficacy of Capsicum annum against Anopheles stephensi and Culex quinquefasciatus. Journal of Vector Borne Diseases, 44, 223.PubMedGoogle Scholar
  29. 29.
    Maurya, P., Mohan, L., Sharma, P., Batabyal, L., & Srivastava, C. (2007). Larvicidal efficacy of Aloe barbadensis and Cannabis sativa against the malaria vector Anopheles stephensi (Diptera: Culicidae). Entomological Research, 37(3), 153–156.CrossRefGoogle Scholar
  30. 30.
    Miranda, C., Stevens, J., Helmrich, A., Henderson, M., Rodriguez, R., Yang, Y.-H., Deinzer, M., Barnes, D., & Buhler, D. (1999). Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines. Food and Chemical Toxicology, 37(4), 271–285.CrossRefPubMedGoogle Scholar
  31. 31.
    Molyneux, D. H., Hotez, P. J., Fenwick, A., Newman, R. D., Greenwood, B., & Sachs, J. (2009). Neglected tropical diseases and the Global Fund. The Lancet, 373(9660), 296–297.CrossRefGoogle Scholar
  32. 32.
    Narayanan Ravisankar, C. S., Sooriamuthu Seeni, Jerrine Joseph, Nanjian Raaman (2014) GC-MS analysis and anticancer activity of methanol extract of leaves of Hypericum hookerianum Wight & Arn International Journal of Pharmacy and Pharmaceutical Sciences 6, 515–519.Google Scholar
  33. 33.
    Newberry, G. D., Bain, O. G., Dyer, C. D. and Sterzi, D. (2017) Pesticide and a method of controlling a wide variety of pests. Google Patents.Google Scholar
  34. 34.
    Pavela, R. (2009). Larvicidal effects of some Euro-Asiatic plants against Culex quinquefasciatus Say larvae (Diptera: Culicidae). Parasitology Research, 105(3), 887–892.CrossRefPubMedGoogle Scholar
  35. 35.
    Poopathi, S., Thirugnanasambantham, K., Mani, C., Mary, K. A., Mary, B. A., & Balagangadharan, K. (2014). Hexamerin a novel protein associated with Bacillus sphaericus resistance in Culex quinquefasciatus. Applied Biochemistry and Biotechnology, 172(5), 2299–2307.CrossRefPubMedGoogle Scholar
  36. 36.
    Reid, B. L., Baker, R. B., Bao, N. N., Koufas, D. A., Kent, G. J. and Baur, P. (2016) Synergistic pesticide compositions. Google Patents.Google Scholar
  37. 37.
    Sachs, J., & Malaney, P. (2002). The economic and social burden of malaria. Nature, 415(6872), 680–685.CrossRefPubMedGoogle Scholar
  38. 38.
    Shaalan, E. A.-S., Canyon, D., Younes, M. W. F., Abdel-Wahab, H., & Mansour, A.-H. (2005). A review of botanical phytochemicals with mosquitocidal potential. Environment International, 31(8), 1149–1166.CrossRefPubMedGoogle Scholar
  39. 39.
    Shu-Chen, C., Ruey-Hong, W., Li-Jie, S., Ming-Chih, C., & Huei, L. (2008). Exposure to mosquito coil smoke may be a risk factor for lung cancer in Taiwan. Journal of Epidemiology, 18(1), 19–25.CrossRefGoogle Scholar
  40. 40.
    Silva, B. A., Ferreres, F., Malva, J. O., & Dias, A. C. (2005). Phytochemical and antioxidant characterization of Hypericum perforatum alcoholic extracts. Food Chemistry, 90(1-2), 157–167.CrossRefGoogle Scholar
  41. 41.
    Su, J., Fu, P., Shen, Y., Zhang, C., Liang, M., Liu, R., Li, H., & Zhang, W. (2008). Simultaneous analysis of flavonoids from Hypericum japonicum Thunb. ex Murray (Hypericaceae) by HPLC-DAD–ESI/MS. Journal of Pharmaceutical and Biomedical Analysis, 46(2), 342–348.CrossRefPubMedGoogle Scholar
  42. 42.
    Taubes, G. (1997). A mosquito bites back. New York Times Magazine, 24, 40–46.Google Scholar
  43. 43.
    Unal, E. L., Mavi, A., Kara, A. A., Cakir, A., Şengül, M., & Yildirim, A. (2008). Antimicrobial and antioxidant activities of some plants used as remedies in Turkish traditional medicine. Pharmaceutical Biology, 46(3), 207–224.CrossRefGoogle Scholar
  44. 44.
    WHO. (2005) World Health Organization: Guidelines for laboratory and field esting of mosquito larvicides. 2005, WHO/CDS/WHOPES/GCPP/2005.Geneva: WHO; 2005.Google Scholar
  45. 45.
    Yang, Y.-C., Lee, S.-G., Lee, H.-K., Kim, M.-K., Lee, S.-H., & Lee, H.-S. (2002). A piperidine amide extracted from Piper longum L. fruit shows activity against Aedes aegypti mosquito larvae. Journal of Agricultural and Food Chemistry, 50(13), 3765–3767.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sreedev Puthur
    • 1
  • A. N Anoopkumar
    • 1
  • Sharrel Rebello
    • 1
  • Embalil Mathachan Aneesh
    • 2
    Email author
  1. 1.Communicable Disease Research LaboratorySt. Joseph’s College, IrinjalakudaThrissurIndia
  2. 2.Department of ZoologySt.Joseph’s College, IrinjalakudaThrissurIndia

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